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Kidney outcomes with SGLT2is for type 2 diabetes patients: does background treatment with metformin or RASis matter?

Kah Suan Chong1, Yi-Hsin Chang1,2, Meng-Hsuan Lin3

  • 1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Frontiers in Endocrinology
|July 12, 2024
PubMed
Abstract

Insights

Concomitant use of metformin or renin-angiotensin system inhibitors (RASis) does not alter kidney outcomes in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i). This real-world evidence confirms SGLT2i safety profiles are not affected by these common co-therapies.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Real-world evidence on the combined effects of metformin and renin-angiotensin system inhibitors (RASis) with sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney outcomes is limited.
  • Understanding these interactions is crucial for optimizing treatment strategies in type 2 diabetes (T2D).

Purpose of the Study:

  • To investigate whether concomitant use of metformin or RASis modifies SGLT2i-associated kidney outcomes in patients with T2D.
  • To provide real-world data on the safety and efficacy of SGLT2i in combination with common antihyperglycemic and antihypertensive agents.

Main Methods:

  • Retrospective analysis of three electronic health record databases (May 2016 - December 2017).
  • SGLT2i users were categorized based on concomitant metformin or RASI use.
  • Propensity score matching and meta-analysis were employed to evaluate mean estimated glomerular filtration rate (eGFR) change and time to eGFR reductions (30%, 40%, 50%).

Main Results:

  • After propensity score matching, significant cohorts of SGLT2i users with and without metformin/RASis were analyzed.
  • While an initial eGFR dip was observed, neither metformin nor RASI use significantly altered SGLT2i-associated eGFR reductions at 30%, 40%, or 50% thresholds.
  • Hazard ratios for eGFR reductions did not show significant differences between groups (e.g., 30% eGFR reduction: HR 1.02 [0.87-1.20] for metformin, HR 1.09 [0.92-1.31] for RASis).

Conclusions:

  • Concomitant use of metformin or RASis does not modify kidney outcomes associated with SGLT2i therapy in patients with T2D.
  • These findings support the established safety profile of SGLT2 inhibitors, irrespective of concurrent metformin or RASI treatment.
  • Real-world data confirms that common co-medications do not negatively impact the renal protective effects of SGLT2i.
Keywords:
estimated glomerular filtration ratekidney functionmetforminrenin-angiotensin system inhibitorssodium-glucose cotransporter-2 inhibitors

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